Obstructive sleep apnea (OSA) is a common medical condition that occurs in a considerable percentage of the population. Substantial evidence shows that patients with OSA have an increased incidence of hypertension compared with individuals without OSA, and that OSA is a risk factor for the development of hypertension. It is established that OSA may be implicated in stroke and transient ischemic attacks. OSA is associated with coronary heart disease, heart failure, and cardiac arrhythmias. Pulmonary hypertension may be associated with OSA, especially in patients with pre-existing pulmonary disease. Although the exact cause that links OSA with cardiovascular disease is unknown, there is evidence that OSA is associated with a group of proinflammatory and prothrombotic factors that have been identified as important in the development of atherosclerosis. OSA is associated with increased daytime and nocturnal sympathetic activity. Autonomic abnormalities seen in patients with OSA include increased resting heart rate, decreased R-R interval variability, and increased blood pressure variability. Both atherosclerosis and OSA are associated with endothelial dysfunction, increased C-reactive protein, interleukin 6, fibrinogen, plasminogen activator inhibitor, and reduced fibrinolytic activity. OSA has been associated with enhanced platelet activity and aggregation. Leukocyte adhesion and accumulation on endothelial cells are common in both OSA and atherosclerosis. Clinicians should be aware that OSA may be a risk factor for the development of cardiovascular disease.

Introduction: Little is known about the impact of spousal involvement on continuous positive airway pressure (CPAP) adherence. The aim of this study was to determine whether spouse involvement affects adherence with CPAP therapy, and how this association varies with gender. Methods: 194 subjects recruited from Apnea Positive Pressure Long Term Efficacy Study (APPLES) completed the Dyadic Adjustment Scale (DAS). The majority of participants were Caucasian (83%), and males (73%), with mean age of 56 years, mean BMI of 31 kg/m2. & 62% had severe OSA. The DAS is a validated 32-item self-report instrument measuring dyadic consensus, satisfaction, cohesion, and affectional expression. A high score in the DAS is indicative of a person’s adjustment to the marriage. Additionally, questions related to spouse involvement with general health and CPAP use were asked. CPAP use was downloaded from the device and self-report, and compliance was defined as usage > 4 h per night. Results: There were no significant differences in overall marital quality between the compliant and noncompliant subjects. However, level of spousal involvement was associated with increased CPAP adherence at 6 months (p=0.01). After stratifying for gender these results were significant only among males (p=0.03). Three years after completing APPLES, level of spousal involvement was not associated with CPAP compliance even after gender stratification. Conclusion: Spousal involvement is important in determining CPAP compliance in males in the 1st 6 months after initiation of therapy but is not predictive of longer-term adherence. Involvement of the spouse should be considered an integral part of CPAP initiation procedures. Support: HL068060

Background: Obstructive sleep apnea has become recognized as one of the most common, under-diagnosed chronic diseases. Recently studies have shown increased numbers among the pediatric and adolescent population. OSA in children is associated with behavioral problems, poor school achievements, and in severe cases, pulmonary hypertension. OSA is often the Achilles heel of pediatric sedation and analgesic programs; during sedation, children with OSA have an increased vulnerability of their airway undergoing pharyngeal collapse and of having upper airway obstruction. Consequently, pediatric dentists who practice sedation dentistry should exercise extra precautions when treating patients with risk of sleep apnea. Currently there is no screening tool used in pediatric dentistry for diagnosing OSA during the pre-operative appointment or consultation for patients undergoing minimal and moderate oral conscious sedation. The purpose of this study was to develop and test a concise and easy-to-use questionnaire as a screening tool to aid in the diagnosis of OSA in pediatric patients. Materials and Methods: A retrospective chart review of 180 patients under the age of 18, who completed a polysomnogram at the VCU Center for Sleep Medicine between February 2011 and February 2013. A validated adult questionnaire, STOPBANG, was modified using more typical pediatric risk factors for OSA: presence of snoring (S), tonsillar hypertrophy (T1), tiredness; pESS>10 (T2), observed obstruction (O), neuroPsych-behavioral symptoms such as ADHD or daytime irritability (P), BMI percentile for age (B), age at diagnostic screening (A), presence of neuromuscular disorder (N), and presence of genetic/congenital disorder (G). A positive scoring from these variables was measured against the standard OSA measure, Apnea-Hypopnea Index. A multiple logistic regression analysis tested for relationships. Results: There was a statistically significant relationship P= .0007 for the S(T1)OPBANG scale, with a minimum of 4 variables needed to have a sensitivity of 57% and a specificity of 78%. There was also a statistically significant relationship P= .0040 for the S(T2)OPBANG, the cutoff>5 yielding sensitivity=36%, and specificity=90%. Only obstruction, BMI, and age showed a strong significant relationship to OSA. The presence of an obstruction was positively related to apnea (P = 0.0010). Most of the other components had an odds-ratio larger than one (indicating a nominally positive relationship). Conclusions: While both STOPBANG screening tools showed a statistically significant relationship, only obstruction, BMI, and age showed a predictive relationship to OSA. Consequently, consideration of other risk factors may be beneficial for future studies.

Nonalcoholic fatty liver disease (NAFLD) afflicts approximately a quarter of the world’s general population and more than half of the world’s obese population. The disease is characterized by a spectrum of liver pathologies, ranging from simple steatosis or the accumulation of fat within hepatic tissue to steatohepatitis comprised of inflammation and fibrosis, also known as NASH. Simple steatosis is relatively asymptomatic and is considered benign, but NASH poses great risk for advanced forms of liver disease, such as cirrhosis and hepatocellular cancer. Obstructive sleep apnea(OSA) is a respiratory disorder involving the recurrent collapse of the upper airway during sleep. Consequently, the patient experiences constant arousals due to constant blockage followed reopening of the airway. Aside from poor quality and disruption of sleep, chronic intermittent hypoxia (CIH) is also present during OSA. The presence of CIH leaves many vital organs deprived of adequate oxygen to carry out normal physiological function. In response to this hypoxic state, the body upregulates many transcription factors, many of which control inflammatory processes. In recent studies, chronic and recurrent hypoxia generated from OSA has been implicated in the onset and progression of NAFLD. The pathogenesis of NAFLD is believed to be associated with metabolic imbalances, mainly obesity and insulin resistance, both of which also overlap with OSA. These conditions are the main factors in predisposing a patient suffering from OSA to the effects of CIH. Multiple lines of evidence suggest that CIH may accelerate the development of NAFLD through 1) Lipolysis of hepatic adipose tissue and increased hepatic free fatty acids; 2) Upregulation of lipid biosynthetic through CIH; 3) Upregulation of hypoxia-inducible factor 1-alpha by CIH inducing liver inflammation and fibrosis. The primary focus of this thesis will attempt to determine a possible link between OSA and NAFLD. Through citation of prior scientific studies, it will formulate the theory of OSA as a predisposing factor in the heightened risk of NAFLD pathogenesis and development to more severe, terminal stages. Primarily, the review of literature will highlight the metabolic imbalances of obesity and insulin resistance and how each is related to OSA and NAFLD. Ultimately, deposition of fat and inflammation triggered through various chemical factors connected to OSA will depict both the generation and progression of NAFLD.

FundaÃÃo de Amparo à Pesquisa do Estado do Cearà / Introduction: Obstructive Sleep Apnea Syndrome (OSAS) in children, as defined by the American Thoracic Society, is a disorder of breathing during sleep characterized by prolonged partial airway obstruction and/or intermittent complete obstruction (obstructive apnea) that disrupts normal ventilation during sleep and normal sleep patterns. Objective: This study aimed to investigate retrospectively the prevalence of OSAS among children aged 6 to 12 years old, evaluated through polysomnography and sleep questionnaires between 2011 and 2012, analyzing severity, symptoms and associated risk factors. Methods: We evaluated 63 children referred to the Sleep Laboratory of the Dell Childrenâs Hospital in Austin, Texas (USA) with suspition of Sleep Disordered Breathing. The patients were submitted to a pre-sleep questionnaire and to polysomnography. Results: The mean age was 8,8 Â1,9 years old, and 55,6% of the children were male. Children without OSAS accounted for 30,2% of the sample. The OSAS observed in the remainder was mild in 49,2%, moderate in 11,1% and severe in 9,5%. Gender and age were not associated with OSAS. Hispanic and African-American children were at higher risk for OSAS. Twenty two hispanic children presented OSAS ( 88%) and ten African-american children presented OSAS (83,3%). In children with OSAS, the most common symptoms were: snoring (86%), periodic limb movements (64,3%), arousals during sleep (60,5%) and restless sleep (58,1%). Excessive daytime sleepiness was reported in only 33,3% of the patients. Bruxism was more prevalent among the patients without OSAS (52,6%) than in the patients with OSAS (31%). Overweight children were at higher risk for OSAS. Conclusions: Overweight children are at a higher risk for developing OSAS. Hispanic and African American children presented a higher risk for developing OSAS. Age and gender were not associated to the diagnose of OSAS. Bruxism was more prevalent among the children who did not present OSAS. / IntroduÃÃo: Em crianÃas, a SÃndrome da Apneia Obstrutiva do Sono (SAOS) à um distÃrbio respiratÃrio caracterizado por obstruÃÃo parcial prolongada e/ou episÃdios intermitentes de obstruÃÃo completa da via aÃrea superior, que interrompe a ventilaÃÃo normal e o padrÃo normal de sono. Objetivo: Este trabalho buscou investigar a prevalÃncia de SAOS entre crianÃas de seis a doze anos de idade, avaliadas por meio de polissonografia e questionÃrio sobre o sono, no perÃodo de 2011 a 2012, avaliando gravidade, sintomatologia e fatores de risco associados. MÃtodos: Foram estudadas 63 crianÃas encaminhadas ao LaboratÃrio do Sono do Dell Childrenâs Hospital em Austin, Texas (EUA) com suspeita de Transtornos RespiratÃrios do Sono. Os pais preencheram um questionÃrio sobre o sono, jà rotineiramente utilizado como padrÃo para todos os pacientes encaminhados para polissonografia no Dell Childrenâs Hospital (ApÃndice A). Em seguida, as crianÃas foram submetidas ao exame polissonogrÃfico. Resultados: A idade mÃdia foi de 8,8Â1,9 anos, sendo 55,6% das crianÃas do sexo masculino. NÃo apneicos corresponderam a 30,2% dos investigados. SÃndrome da Apneia Obstrutiva do Sono em grau leve ocorreu em 49,2%, moderado em 11,1% e grave em 9,5%. NÃo foi encontrada diferenÃa entre a incidÃncia de SAOS entre meninos e meninas. Observou-se uma associaÃÃo estatisticamente significante entre raÃa e presenÃa/ausÃncia de SAOS, sendo que as crianÃas negras e hispÃnicas apresentaram maior risco de SAOS do que as crianÃas brancas. Entre os hispÃnicos, 88% dos pacientes apresentaram SAOS (n=22); nos negros 83,3% (n=10) e nos brancos 46,7% (n=7). Dentre as crianÃas diagnosticadas com SAOS, os sintomas mais frequentes foram: ronco (86%) movimentos periÃdicos de membros (64,3%), despertares durante o sono (60,5%) e sono agitado (58,1%). SonolÃncia excessiva foi relatada apenas em 33,3% dos casos. O bruxismo foi relatado com maior frequÃncia no grupo sem SAOS (52,6%) do que no grupo de pacientes com diagnÃstico de SAOS (31%). CrianÃas com sobrepeso apresentaram maior risco de desenvolver SAOS (100%) (Testes Qui quadrado e exato de Fisher). ConclusÃes: Sobrepeso à um fator de risco para SAOS. CrianÃas da raÃa hispÃnica e negra apresentaram maior risco a SAOS. Sexo e idade nÃo se associaram a SAOS. O bruxismo foi mais frequentemente relatado por pacientes que nÃo demonstraram SAOS.

Master of Science (Medicine) / Clinical studies have demonstrated an arousal deficit in infants suffering Obstructive Sleep Apnoea (OSA), and that treatment to alleviate the symptoms of OSA appears to reverse the deficit in arousability. Some sudden infant deaths are thought to be contingent upon such an arousal deficit. This research utilised young piglets during early postnatal development, and exposed them to intermittent hypercapnic hypoxia (IHH) as a model of clinical respiratory diseases. Arousal responses of control animals were compared to the animals exposed to IHH. Comparisons were also made between successive exposures on the first and the fourth consecutive days of IHH. Time to arouse after the onset of the respiratory stimulus, and frequency of arousals during recovery, demonstrated that arousal deficits arose after successive exposures and that these were further exacerbated on the fourth study day. After an overnight recovery period, the arousal deficit was apparently dormant, and only triggered by HH exposure. These studies confirm that both acute and chronic deficits can be induced on a background of otherwise normal postnatal development, suggesting that deficits observed in the clinical setting may be a secondary phenomenon.

Hypoxia is a common feature of many respiratory disorders including acute severe asthma, chronic obstructive pulmonary disease and pneumonia. Hypoxia also occurs during sleep - disordered breathing in conditions such as sleep hypoventilation syndrome and sleep apnea. In most respiratory diseases hypoxia is coupled with increased respiratory load. Compensatory protective mechanisms are activated to oppose these impediments to respiration. However, hypoxia is associated with impaired neurocognitive function and recent studies have demonstrated that hypoxia suppresses respiratory load perception in healthy individuals and asthma patients. These recent findings raise the possibility that a variety of protective physiological reflex responses to increased respiratory load may be impaired during periods of hypoxia. The effects of hypoxia on several of these protective responses and possible mechanisms of respiratory sensory depression by hypoxia are explored in the experiments outlined in this thesis. In the first study, the respiratory related evoked potential ( RREP ) was used to investigate the mechanisms underlying hypoxia - induced suppression of respiratory load sensation in healthy individuals. As a positive control the effects of hypoxia on respiratory load perception to inspiratory resistive loads were also measured. The amplitude of the first and second positive peaks ( P1 and P2 ) of the RREP were significantly reduced during hypoxia. P1 is thought to reflect the arrival of the ascending respiratory signals to the somatosensory area of the cortex. The perceived magnitude of externally applied inspiratory resistive loads was also reduced during hypoxia. These data provide further support that hypoxia suppresses respiratory load perception and suggest that this is mediated, at least in part, by suppression of respiratory afferent information prior to its arrival at the cortex. In the second study, the effects of acute sustained hypoxia on the cough reflex threshold and cough tachyphylaxis to inhaled capsaicin were explored in healthy individuals. Acute sustained hypoxia suppressed cough reflex sensitivity to inhaled capsaicin. This finding raises the possibility that the cough reflex, important for protecting the lungs from inhalation or aspiration of potentially injurious substances and for clearing excess secretions, may be impaired during acute exacerbations of hypoxic - respiratory disease. In the third study, reflex responses of the genioglossus and scalene muscles to brief pulses of negative airway pressure were compared between hypoxia and normoxia during wake and sleep in healthy males in the supine position. Cortical RREPs to the same stimuli were also examined under these conditions. The genioglossus is the largest upper airway ( UA ) dilator muscle and can be reflexively augmented in response to negative UA pressure. A diminished response of this muscle during sleep has been postulated to be a contributing mechanism to obstructive sleep apnea ( OSA ) in individuals with an anatomically narrow UA. Cortical activation ( i.e. arousal ) to sudden airway narrowing in OSA is an important protective response to help restore ventilation during an obstructive event. In this study, genioglossus reflex responses to negative pressure pulse stimuli were maintained during mild overnight hypoxia. Conversely, reflex inhibition of the scalene muscle to the same stimuli was prolonged during hypoxia. In addition, a previously undescribed morphology of the genioglossus negative pressure reflex consisting of activation followed by suppression was observed with greater suppression during sleep than wake. The amplitude of the P2 component of the RREP was also significantly reduced during hypoxia. In summary, the potential mechanisms underlying hypoxia - induced suppression of respiratory load sensation and the effects of hypoxia on several protective respiratory responses have been investigated in healthy subjects. The potential implications of these findings for patients with hypoxic - respiratory disease are discussed. / Thesis (Ph.D.)--School of Molecular and Biomedical Science, 2006.

Thesis (Ph. D.)--Case Western Reserve University, 2007. / [School of Medicine] Department of Epidemiology and Biostatistics. Includes bibliographical references. Available online via OhioLINK's ETD Center.

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In recent years, sleep medicine has attracted many interests. Among many sleep disorder problems, the sleep apnea syndrome is of great importance. One of its side effects is its negative influences on cardiovascular system whose function can be monitored by ECG. The regulation of the heart rate is extremely important for human body. In general, the heart rate variability is controlled by the balance of the sympathetic and the parasympathetic systems whose functions can be influenced by sleep apnea. This work tries to establish the relation between the heart rate variability and AHI (Apnea & hypopnea index). Through the statistical methods, we analyze how the sleep apnea influences the low frequency (LF) and high frequency components of the RR intervals. With BMI, age and AHI as the independent variables, we set up the regression model to predict LF/HF Our results demonstrate that, for men, the linear relationship between the LF/HF and AHI is statistically significant when AHI is higher than 45. This results may shed some light on developing HRV based diagnosis method for sleep apnea.